期刊
BRAIN PATHOLOGY
卷 21, 期 3, 页码 321-329出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1750-3639.2010.00449.x
关键词
Alzheimer's disease; amyloid; Cos-7 cells; oleic acid; plaques; transgenic mice
资金
- London and Middlesex Alzheimer's Association
- Canadian Institutes of Health Research [MOP49546]
- Alberta Heritage Foundation for Medical research
- Ontario Mental Health Foundation
Several lines of evidence support protective as well as deleterious effects of oleic acid (OA) on Alzheimer's disease (AD) and other neurological disorders; however, the bases of these effects are unclear. Our investigation demonstrates that amyloid precursor protein (APP) 695 transfected Cos-7 cells supplemented with OA have reduced secreted amyloid-beta (A beta) levels. An early-onset AD transgenic mouse model expressing the double-mutant form of human APP, Swedish (K670N/M671L) and Indiana (V717F), corroborated our in vitro findings when they were fed a high-protein, low-fat (18% reduction), cholesterol-free diet enriched with OA. These mice exhibited an increase in A beta 40/A beta 42 ratio, reduced levels of beta-site APP cleaving enzyme (BACE) and reduced presenilin levels along with reduced amyloid plaques in the brain. The decrease in BACE levels was accompanied by increased levels of a non-amyloidogenic soluble form of APP (sAPP alpha). Furthermore, the low-fat/+OA diet resulted in an augmentation of insulin-degrading enzyme and insulin-like growth factor-II. These results suggest that OA supplementation and cholesterol intake restriction in a mouse model of AD reduce AD-type neuropathology.
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